Obesity-induced mesenteric PVAT remodelling is sexually dimorphic, but not driven by ovarian hormones

作者：Lisa Ivatt, Mhairi Paul, Allende Miguelez-Crespo, Patrick W. F. Hadoke, Matthew A. Bailey, Ruth Morgan, Mark Nixon · 发表于：Cardiovascular Diabetology · 年份：2025 · DOI：10.1186/s12933-025-02596-w · 被引用次数：6 · 研究领域：Cardiovascular Disease and Adiposity、Bariatric Surgery and Outcomes、Adipokines, Inflammation, and Metabolic Diseases

BACKGROUND: Obesity, a major risk factor for cardiovascular disease (CVD), is associated with hypertension and vascular dysfunction. Perivascular adipose tissue (PVAT), a metabolically active tissue surrounding blood vessels, plays a key role in regulating vascular tone. In obesity, PVAT becomes dysregulated which may contribute to vascular dysfunction; how sex impacts the remodelling of PVAT and thus the altered vascular contractility during obesity is unclear. OBJECTIVE: To investigate sex-specific PVAT dysregulation in the setting of obesity as a potential driver of sex differences in vascular pathologies and CVD risk. METHODS: Adult male and female C57Bl/6J mice were fed an obesogenic high-fat diet (HFD) or regular chow for 16 weeks. Mesenteric PVAT (mPVAT) was isolated for RNA-sequencing and histological analysis, and mesenteric arteries were isolated for assessment of vascular function by wire myography. In a separate study, female mice were subjected to bilateral ovariectomy prior to dietary intervention to determine the contribution of ovarian hormones to PVAT dysregulation. RESULTS: Transcriptomic analysis of mPVAT revealed sexually dimorphic responses to HFD, with upregulation of extracellular matrix (ECM) remodelling pathways in male but not female mice. Histological and RT-qPCR approaches demonstrated increased collagen deposition and ECM remodelling in mPVAT from obese male compared with obese female mice. Assessment of vascular function in mesenteric arteries -/...